Introduction
: Ischemic stroke (IS) makes up a significant proportion of all strokes, of which large vessel occlusions (LVO) are the most debilitating type. The current clinical standard‐of‐care for IS includes mechanical thrombectomy with stent retrievers. One of the impediments to the success of SR intervention is endothelial injury (EI), which can occur in approximately 30% of cases and impedes vessel reperfusion. Since successful reperfusion of the occluded vessel is instrumental in survival and patient recovery, it is imperative to reduce device injury‐based complications such as vasospasm, and to improve patient outcomes.
Methods
: In this work, our hypothesis is that EI can be reduced by investigating the mechanisms of stent retriever‐induced injury in vitro using live cell 3D cerebrovascular models. Using true‐scale cerebrovascular phantoms with lumen diameter approximately 4 mm created using 3D printing and PDMS casting, Human Umbilical Vein Endothelial Cells (HUVECs) were seeded on the luminal surface. The in vitro models were coated with fibronectin (density 4 µgrams/cm2) to encourage cell adhesion, and were divided into control and treated samples (n = 3 each). Mechanical thrombectomy was performed using two different clinically used SR (Trevo XP PROVUE 3 × 20 mm and Trevo XP PROVUE 6 × 30 mm) to investigate the extent of stent retriever size on EI on the same diameter lumen. Following thrombectomy, the cerebrovascular models were fixed and stained with immunofluorescent dyes (DAPI, Phalloidin and VE cadherin antibody) and imaged using transmitted light, confocal microscopy and scanning electron microscopy. For quantitative assessment, real time PCR was performed on both control and treated samples.
Results
: All models were initially confluent and functional, as assessed by immunofluorescent staining (Figure 1 A and B). All treated samples demonstrated EI and endothelial damage, as evidenced by loss of endothelial cell coverage, denuding of the models, stripping / clumping of endothelial cells into non‐physiological three dimensional structures and physical scratching of the in vitro model (Figure 1 C and D). Sizing of stent retriever had a strong influence on the effects on the endothelium, with larger sizes causing more damage.
Conclusions
: A significant knowledge gap exists in understanding the factors responsible for disruption of the endothelium during mechanical thrombectomy. Using a 3D in vitro platform of cerebrovasculature, we demonstrated that endothelial damage occurs during thrombectomy using stent retrievers. A parameteric investigation is currently ongoing that characterizes the influence of vessel lumen diameter, stent retriever size, number of passes and patient specific vasculature. This work can provide guidelines for optimal stent retriever devices to be used where possible, ultimately reducing EI and improving outcomes of ischemic stroke treatment.
Acute ischemic stroke thrombi have an outer shell that impairs fibrinolysis